A rapid and simple high-pressure liquid chromatographic method was developed for the simultaneous determination of plasma levels of procainamide and its major metabolite, N-acetonitrile, and the supernate was chromatographed on a cation-exchange column. The assay can be carried out on as little as 20 microliter of plasma and requires only about 7 min for each sample. No interference was found in plasma samples from cardiac patients receiving procainamide. This method is simple, fast, and useful for routine therapeutic monitoring and for pharmacokinetic studies procainamide and its metabolite.